Circulating levels of secretory- and lipoprotein-associated phospholipase A2 activities: relation to atherosclerotic plaques and future all-cause mortality.

ABSTRACT

AIMS: Secretory- and lipoprotein-associated phospholipases A2 (sPLA2 and Lp-PLA2) are enzymes both suggested to be of importance for atherosclerosis. We investigated relationships between the activities of these enzymes in the circulation and atherosclerosis as well as future clinical events. METHODS AND RESULTS: The population-based Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study included 1016 randomly selected subjects, all aged 70. The prevalence of carotid artery plaques was recorded by ultrasound (n= 954), and arterial stenosis was assessed by whole-body magnetic resonance angiography (WBMRA, n= 302). Secretory-associated phospholipase A2 [odds ratio 1.23 for 1 SD increase, 95% confidence interval (CI) 1.05-1.44, P= 0.007], but not Lp-PLA2 (P= 0.26), activity was significantly related to carotid atherosclerosis and to the amount of stenosis at WBMRA (P= 0.006) following adjustment for multiple risk factors (waist circumference, serum triglycerides, body mass index, C-reactive protein, high density lipoprotein-C, low density lipoprotein-C, triglycerides, GFR, fasting glucose, blood pressure, statin use, and exercise habits). Secretory-associated phospholipase A2 [hazard ratio (HR) 1.45 for 1 SD increase, 95% CI 1.15-1.84, P= 0.001], but not Lp-PLA2 (HR 0.95, P= 0.55), activity was a significant risk factor for all-cause mortality (114 had died) during 7.0 years follow-up after adjustment for the risk factors described above. In a sample of 1029 post-myocardial infarction (MI) patients (French registry of Acute ST-elevation and non-ST-elevation Myocardial Infarction), sPLA2 (adjusted HR 1.32 for 1 unit increase, 95% CI 1.02-1.71, P= 0.036), but not Lp-PLA2 (HR 1.03, P= 0.90), activity predicted death or recurrent MI during 1-year follow-up (n= 136 cases). CONCLUSION: sPLA2 activity was related to atherosclerosis and predicted all-cause mortality in a sample of elderly subjects, as well as death or MI in post-MI patients.